FDA has granted priority review for Genentech’s supplemental Biologics License Application for Tecentriq (atezolizumab) plus chemotherapy, Abraxane (albumin-bound paclitaxel; nab-paclitaxel) for the first-line treatment of unresectable locally advanced or metastatic triple-negative breast cancer in people whose disease expresses the PD-L1 protein, as determined by PD-L1 biomarker testing.
FDA is expected to make a decision on approval by March 12, 2019. A
The sBLA is based on data from the phase III IMpassion130 study, which was presented at the European Society for Medical Oncology Congress and published in the New England Journal of Medicine in October 2018. Results demonstrate Tecentriq plus nab-paclitaxel as an first-line treatment for unresectable locally advanced or metastatic TNBC significantly reduced the risk of disease worsening or death (progression-free survival) compared with nab-paclitaxel alone in all randomized patients (intention-to-treat) (median PFS=7.2 vs. 5.5 months; hazard ratio [HR]=0.80, 95% CI: 0.69-0.92, p=0.0025) and the PD-L1-positive population (median PFS=7.5 vs. 5.0 months; HR=0.62, 95% CI: 0.49-0.78, p<0.0001), a subgroup determined by PD-L1 biomarker testing.
At this interim analysis, statistical significance was not met for overall survival in the ITT population (median OS=21.3 vs. 17.6 months; HR=0.84, 95% CI: 0.69-1.02, p=0.0840), but the combination showed a clinically meaningful OS improvement in the PD-L1-positive population (median OS=25.0 vs. 15.5 months; HR=0.62, 95% CI: 0.45-0.86).
Due to the hierarchical statistical design, results in the PD-L1-positive population were not formally tested for statistical significance. Follow-up will continue until the next planned analysis. Safety in the Tecentriq plus nab-paclitaxel arm appeared consistent with the known safety profiles of the individual medicines, and no new safety signals were identified with the combination. Serious adverse events were reported in 23 percent of people who received Tecentriq plus nab-paclitaxel compared to 18 percent of people who received nab-paclitaxel alone.
Currently, Genentech has seven ongoing phase III studies investigating Tecentriq in TNBC, including early and advanced stages of the disease. If approved, this Tecentriq combination would be the first cancer immunotherapy regimen for the treatment of PD-L1-positive, metastatic TNBC.
The IMpassion130 study is a phase III, multicenter, randomized, double-blind study evaluating the efficacy, safety and pharmacokinetics of Tecentriq plus nab-paclitaxel compared with placebo plus nab-paclitaxel in people with unresectable locally advanced or metastatic TNBC who have not received prior systemic therapy for metastatic breast cancer. The study enrolled 902 people who were randomized equally (1:1). The co-primary endpoints are PFS per investigator assessment (RECIST 1.1) and OS. PFS and OS were assessed in all randomized patients (ITT) and in the PD-L1-positive population. Secondary endpoints include objective response rate, duration of response and time to deterioration in Global Health Status/Health-Related Quality of Life.
In a year that brought us new KRAS-inhibiting drugs, deepened our understanding of HER2 in breast cancer, and highlighted new potential for mRNA vaccines, the cancer field was also rocked by uncertainty of the future of research funding, equity in cancer delivery, and the integrity of review at FDA.
